THERAPEUTIC OPTIONS FOR REFRACTORY EPILEPSY: A LITERATURE REVIEW

Abstract

Epilepsy affects about 50 million people worldwide and is characterized by recurrent seizures resulting from excessive and synchronous neural discharges. These patients have a higher risk of trauma, psychiatric disorders, reduced quality of life, morbidity, and premature mortality, representing a significant public health challenge. In this context, new therapeutic options for refractory epilepsy have been studied, including brain stimulation, cannabidiol, transcranial electrical stimulation, dietary approaches, and novel drugs such as levetiracetam, soticlestat, fenfluramine, padsevonil, and cenobamate. The aim of this review was to analyze the efficacy and tolerability of these approaches in patients with unmet therapeutic needs. A search was conducted in the Lilacs and PubMed databases using the descriptors “drug resistant epilepsy” and “treatment” with the operator “AND,” including open-access articles published between 2014 and 2019, restricted to clinical trials and controlled clinical trials. A total of 32 studies were selected. Among them, 10 demonstrated that cannabidiol and its derivatives are safe, well tolerated, and effective in reducing seizures, despite side effects such as somnolence and diarrhea. Five studies highlighted brain stimulation as safe and effective. Seven studies reported favorable outcomes with dietary therapies, mainly as adjuvant treatment. Among the drugs, fenfluramine, soticlestat, cenobamate, eslicarbazepine, and levetiracetam showed benefits, whereas ataluren, natalizumab, padsevonil, and triheptanoin did not achieve significant results. In conclusion, cannabidiol, brain stimulation, and ketogenic diets appear to be promising therapies, and some recently developed drugs show potential. However, further studies are still needed to expand effective therapeutic options for the management of refractory epilepsy.